摘要：β-Lapachone (β-Lap) is a promising orthonaphthoquinone drug for cancer treatment and has been inclinical trials. Its application is constrained by the low aqueoussolubility, and severe side effects. Even prodrug designation isan effective approach to render it with tumor selectivity, it islimited by the lack of modifiable groups on β-Lap. Herein, anovel azo bond primary cleavage and carbon–carbon (C–C)bond secondary cleavage-based polymeric β-Lap prodrug(Azo-Lap NP) is designed, in which the self-immolated paraaminobenzyl linker is connected to poly(L-glutamic acid)(PGlu) via azo linkage and the responsive drug release of β-Lapagainst tumors can be achieved under high NAD(P)H:quinoneoxidoreductase 1 (NQO1) expression and low pH environmentin tumors. The effective covalent loading of β-Lap by Azo-LapNPs permitted a high administration dose of β-Lap and enabled significant tumor retention time. Moreover, Azo-LapNPs markedly reduced the side effects of β-Lap by avoidinghemolysis and the production of methemoglobin. The safety ofAzo-Lap NPs administration is validated in the antitumorexperiment of mice. In the 4T1 model, Azo-Lap NPs exhibiteda markedly higher tumor suppression rate than β-Lap. Thiswork provides an effective and safe polymeric prodrug fortumor selective delivery of β-Lap.

摘要：Liver injury is a common cause of drug approval withdrawal during drug development,pre-clinical research,and clinical *** not properly treated,patients with severe liver injury can suffer from acute liver failure or even ***,utilization of the convenient in vitro hepatotoxicity assessment model for early detection of drug-induced hepatotoxicity is vital for drug development and safe personalized ***(e.g.,hydrogels,nanofibers,decellularized liver matrix)and bioengineering technologies(e.g.,microarrays,micropatterns,3D printing,and microfluidics)have been applied for in vitro hepatotoxicity assessment *** review summarizes the structure and functions of the liver as well as the components of in vitro hepatotoxicity assessment *** addition,it highlights the latest advances in developing hepatotoxicity models with the ultimate goal of further clinical translation.

摘要：Combination antiretroviral therapy(ART)reduced AIDS-related mortality and increased survival among patients living with HIV by interrupting HIV replication,enhancing immune recovery,and preventing the onset of opportunistic infections[1].In China,ART has rapidly been scaled up since the beginning of the National Free Antiretroviral treatment Program(NFATP)in 2003[2].By the end of 2016,489,411 individuals diagnosed with HIV were receiving free antiretroviral treatment in *** is firmly committed to reducing overall AIDS-related mortality and HIV incidence within the ***,similar to other low-and middle-income countries,the NFATP is challenged by high mortality and attrition shortly after patients initiate ART[3].